Genetic and Anthropometric Interplay: How Waist-to-Hip Ratio Modulates LDL-c Levels in Mexican Population.

BACKGROUND/OBJECTIVES: Genetic factors contribute to the physiopathology of obesity and its comorbidities. This study aimed to investigate the association of the SNPs ABCA1 (rs9282541), ADIPOQ (rs2241766), FTO (rs9939609), GRB14 (rs10195252), and LEPR (rs1805134) with various clinical, anthropometric, and biochemical variables. METHODS: The study included 396 Mexican mestizo individuals with obesity and 142 individuals with normal weight. Biochemical markers were evaluated from peripheral blood samples, and SNP genotyping was performed using PCR with TaqMan probes. A genetic risk score (GRS) was computed using an additive model. RESULTS: No significant associations were found between the SNPs ABCA1, ADIPOQ, FTO, and LEPR with obesity. However, the T allele of the GRB14 SNP was significantly associated with obesity (χ2 = 5.93, p = 0.01; OR = 1.52; 95% CI: 1.08-2.12). A multivariate linear regression model (adjusted R-squared: 0.1253; p < 0.001) predicting LDL-c levels among all participants (n = 538) identified significant (p < 0.05) beta coefficients for several anthropometric and biochemical variables, as well as for the GRS. Additionally, the interaction between the GRS and the waist-to-hip ratio (WHR) showed a negative beta coefficient (BC = -26.5307; p = 0.014). Participants with a WHR < 0.839 showed no effect of GRS on LDL-c concentration, while those with a WHR > 0.839 exhibited a greater effect of GRS (~9) at lower LDL-c concentrations (~50 mg/dL) and a lesser effect of GRS (~7) at higher LDL-c concentrations (~250 mg/dL). CONCLUSIONS: A significant interaction between genetics and WHR influences LDL-c in Mexicans, which may contribute to the prevention and clinical management of dyslipidemia and cardiovascular disease.

Analysis of Sigma-1 Receptor Antagonist BD1047 Effect on Upregulating Proteins in HIV-1-Infected Macrophages Exposed to Cocaine Using Quantitative Proteomics.

HIV-1 infects monocyte-derived macrophages (MDM) that migrate into the brain and secrete virus and neurotoxic molecules, including cathepsin B (CATB), causing cognitive dysfunction. Cocaine potentiates CATB secretion and neurotoxicity in HIV-infected MDM. Pretreatment with BD1047, a sigma-1 receptor antagonist, before cocaine exposure reduces HIV-1, CATB secretion, and neuronal apoptosis. We aimed to elucidate the intracellular pathways modulated by BD1047 in HIV-infected MDM exposed to cocaine. We hypothesized that the Sig1R antagonist BD1047, prior to cocaine, significantly deregulates proteins and pathways involved in HIV-1 replication and CATB secretion that lead to neurotoxicity. MDM culture lysates from HIV-1-infected women treated with BD1047 before cocaine were compared with untreated controls using TMT quantitative proteomics, bioinformatics, Lima statistics, and pathway analyses. Results demonstrate that pretreatment with BD1047 before cocaine dysregulated eighty (80) proteins when compared with the infected cocaine group. We found fifteen (15) proteins related to HIV-1 infection, CATB, and mitochondrial function. Upregulated proteins were related to oxidative phosphorylation (SLC25A-31), mitochondria (ATP5PD), ion transport (VDAC2-3), endoplasmic reticulum transport (PHB, TMED10, CANX), and cytoskeleton remodeling (TUB1A-C, ANXA1). BD1047 treatment protects HIV-1-infected MDM exposed to cocaine by upregulating proteins that reduce mitochondrial damage, ER transport, and exocytosis associated with CATB-induced neurotoxicity.

Marchantia polymorpha GOLDEN2-LIKE transcriptional factor; a central regulator of chloroplast and plant vegetative development.

The GOLDEN2-LIKE (GLK) transcription factors act as a central regulatory node involved in both developmental processes and environmental responses. Marchantia polymorpha, a basal terrestrial plant with strategic evolutionary position, contains a single GLK representative that possesses an additional domain compared to spermatophytes. We analyzed the role of MpGLK in chloroplast biogenesis and development by altering its levels, preforming transcriptomic profiling and conducting chromatin immunoprecipitation. Decreased MpGLK levels impair chloroplast differentiation and disrupt the expression of photosynthesis-associated nuclear genes, while overexpressing MpGLK leads to ectopic chloroplast biogenesis. This demonstrates the MpGLK functions as a bona fide GLK protein, likely representing an ancestral GLK architecture. Altering MpGLK levels directly regulates the expression of genes involved in Chl synthesis and degradation, similar to processes observed in eudicots, and causes various developmental defects in Marchantia, including the formation of dorsal structures such as air pores and gemma cups. MpGLK, also directly activates MpMAX2 gene expression, regulating the timing of gemma cup development. Our study shows that MpGLK functions as a master regulator, potentially coupling chloroplast development with vegetative reproduction. This illustrates the complex regulatory networks governing chloroplast function and plant development communication and highlight the evolutionary conservation of GLK-mediated regulatory processes across plant species.

Genetic Influence on Capsaicin Tolerance: Precision Nutrition Implications for Obesity Handling.

INTRODUCTION: It has been suggested that capsaicin (CAP), a major pungent component in chili peppers, can be used as an anti-obesity ingredient due to effects on energy metabolism, but evidence is not consistent. Genetics may account for differences in CAP tolerance and its impact on adiposity status. The aim of this study was to systematically review current evidence concerning the role of genetic polymorphisms influencing CAP tolerance. METHODS: The present systematic review analyzed and synthesized available evidence concerning associations between genetic polymorphisms and CAP tolerance following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. Databases such as PubMed/MEDLINE, Cochrane, Scopus, Google Scholar, SciELO, and LILACS were screened. Out of 228 publications identified, only 6 meet inclusion criteria and were finally included in the final report. RESULTS: Overall, a total of 28 single nucleotide polymorphisms were associated with several CAP tolerance traits including sensitivity to burning/stinging, heat pain, and cough reactions, and detection of bitter taste thresholds. These genetic variants were located within 6 genes involved in key physiological processes such synthesis of tetrahydrobiopterin and nitric oxide production (GCH1), CAP uptake and transduction of thermal stimuli (TRPV1), and bitter taste perception (TAS2R38, TAS2R3, TAS2R4, and TAS2R5). CONCLUSION: There is evidence about the influence of genetic polymorphisms on CAP tolerance by affecting nociceptive signaling, CAP binding, and bitter tasting. This knowledge may facilitate the design and implementation of innovative CAP-based nutrigenetic strategies for a more precise clinical management of obesity.

Tree demographic strategies largely overlap across succession in Neotropical wet and dry forest communities.

Secondary tropical forests play an increasingly important role in carbon budgets and biodiversity conservation. Understanding successional trajectories is therefore imperative for guiding forest restoration and climate change mitigation efforts. Forest succession is driven by the demographic strategies-combinations of growth, mortality and recruitment rates-of the tree species in the community. However, our understanding of demographic diversity in tropical tree species stems almost exclusively from old-growth forests. Here, we assembled demographic information from repeated forest inventories along chronosequences in two wet (Costa Rica, Panama) and two dry (Mexico) Neotropical forests to assess whether the ranges of demographic strategies present in a community shift across succession. We calculated demographic rates for >500 tree species while controlling for canopy status to compare demographic diversity (i.e., the ranges of demographic strategies) in early successional (0-30 years), late successional (30-120 years) and old-growth forests using two-dimensional hypervolumes of pairs of demographic rates. Ranges of demographic strategies largely overlapped across successional stages, and early successional stages already covered the full spectrum of demographic strategies found in old-growth forests. An exception was a group of species characterized by exceptionally high mortality rates that was confined to early successional stages in the two wet forests. The range of demographic strategies did not expand with succession. Our results suggest that studies of long-term forest monitoring plots in old-growth forests, from which most of our current understanding of demographic strategies of tropical tree species is derived, are surprisingly representative of demographic diversity in general, but do not replace the need for further studies in secondary forests.

Personalized medicine and nutrition in hepatology for preventing chronic liver disease in Mexico.

Chronic liver disease is a global health issue. Patients with chronic liver disease require a fresh approach that focuses on the genetic and environmental factors that contribute to disease initiation and progression. Emerging knowledge in the fields of Genomic Medicine and Genomic Nutrition demonstrates differences between countries in terms of genetics and lifestyle risk factors such as diet, physical activity, and mental health in chronic liver disease, which serves as the foundation for the implementation of Personalized Medicine and Nutrition (PerMed-Nut) strategies. Most of the world's populations have descended from various ethnic groupings. Mexico's population has a tripartite ancestral background, consisting of Amerindian, European, and African lineages, which is common across Latin America's regional countries. The purpose of this review is to discuss the genetic and environmental components that could be incorporated into a PerMed-Nut model for metabolic-associated liver disease, viral hepatitis B and C, and hepatocellular carcinoma in Mexico. Additionally, the implementation of the PerMed-Nut approach will require updated medicine and nutrition education curricula. Training and equipping future health professionals and researchers with new clinical and investigative abilities focused on preventing liver illnesses in the field of genomic hepatology globally is a vision that clinicians and nutritionists should be concerned about.

Low Dietary Betaine Intake Is Associated with Increased Blood Cholesterol in Mexican Subjects.

BACKGROUND: Betaine, an osmolyte derivative of the metabolite choline and the amino acid glycine, acts as a methyl donor in the conversion of homocysteine to methionine and is involved in the maintenance of adequate lipid metabolism. There is growing evidence for the role of betaine in the development of various lipid-related diseases, including dyslipidemia and cardiovascular risk. This study aimed to analyze associations between betaine intake and blood lipid profiles in Mexican subjects. METHODS: A total of 212 adults were randomly recruited in the city of Tijuana, Baja California, Mexico. Betaine intake was estimated using Nutritionist Pro software. Body composition and metabolic measurements were obtained by conventional methods. In the total sample, the average intake of betaine was 14.32 mg/d. Individuals were categorized into three groups according to tertiles of betaine consumption: tertile/group 1 (<4.16 mg/d), tertile/group 2 (4.16-12.02 mg/d), and tertile/group 3 (>12.02 mg/d). RESULTS: Compared to group 3, subjects within group 1 had higher serum levels of total cholesterol (p = 0.001), LDL-c (p = 0.026), and non-HDL-c (p = 0.021). In addition, significant negative Pearson correlations were found between betaine intake and the serum levels of total cholesterol (r = -0.432, 95% CI, -0.684, -0.185, p = 0.001), LDL-c (r = -0.370, 95% CI, -0.606, -0.134, p = 0.002), and non-HDL-c (r = -0.351, 95%CI, -0.604, -0.098, p = 0.007). CONCLUSIONS: Our results show that a low intake of betaine is associated with elevated blood cholesterol levels in Mexican subjects. On this basis, betaine consumption could be used as an additional dietary measure for cardiovascular care. However, additional studies are required to confirm our results in other Mexican regions as well as in other populations worldwide.

Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus.

Globally, type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders. T2DM physiopathology is influenced by complex interrelationships between genetic, metabolic and lifestyle factors (including diet), which differ between populations and geographic regions. In fact, excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM, whereas habitual intakes of plant-based healthy diets usually exert a protective effect. Moreover, genomic studies have allowed the characterization of sequence DNA variants across the human genome, some of which may affect gene expression and protein functions relevant for glucose homeostasis. This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression, some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions. Also, novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations. Furthermore, progresses in other omics areas (epigenomics, metagenomics, proteomics, and metabolomics) are improving current understanding of genetic insights in T2DM clinical outcomes. Although more investigation is still needed, the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening, prevention, diagnosis, management, and prognosis of T2DM through precision nutrition.

Incomplete recovery of tree community composition and rare species after 120 years of tropical forest succession in Panama.

Determining how fully tropical forests regenerating on abandoned land recover characteristics of old-growth forests is increasingly important for understanding their role in conserving rare species and maintaining ecosystem services. Despite this, our understanding of forest structure and community composition recovery throughout succession is incomplete, as many tropical chronosequences do not extend beyond the first 50 years of succession. Here, we examined trajectories of forest recovery across eight 1-hectare plots in middle and later stages of forest succession (40-120 years) and five 1-hectare old-growth plots, in the Barro Colorado Nature Monument (BCNM), Panama. We first verified that forest age had a greater effect than edaphic or topographic variation on forest structure, diversity and composition and then corroborated results from smaller plots censused 20 years previously. Tree species diversity (but not species richness) and forest structure had fully recovered to old-growth levels by 40 and 90 years, respectively. However, rare species were missing, and old-growth specialists were in low abundance, in the mid- and late secondary forest plots, leading to incomplete recovery of species composition even by 120 years into succession. We also found evidence that dominance early in succession by a long-lived pioneer led to altered forest structure and delayed recovery of species diversity and composition well past a century after land abandonment. Our results illustrate the critical importance of old-growth and old secondary forests for biodiversity conservation, given that recovery of community composition may take several centuries, particularly when a long-lived pioneer dominates in early succession. Abstract in Spanish is available with online material.

Determinar en que medida los bosques tropicales que se regeneran en tierras abandonadas recuperan las características de los bosques primarios es cada vez más importante para comprender su papel en la conservación de especies raras y el mantenimiento de los servicios ecosistémicos. A pesar de ello, nuestro entendimiento sobre la recuperación de la estructura del bosque y la composición de la comunidad a lo largo de la sucesión es incompleta, ya que muchas cronosecuencias tropicales no van más allá de los primeros 50 años de sucesión. En este estudio, investigamos las trayectorias de recuperación del bosque en ocho parcelas de 1 hectárea en estadíos medios y tardíos de la sucesión forestal (40­120 años) y cinco parcelas de 1 hectárea de bosque primario, en el Monumento Natural Barro Colorado (MNBC), Panamá. En primer lugar, verificamos que la edad del bosque tenía un mayor efecto que la variación edáfica o topográfica en la estructura, diversidad y composición del bosque y luego corroboramos los resultados de parcelas más pequeñas estudiadas 20 años antes. La diversidad de especies arbóreas, pero no la riqueza de especies, y la estructura forestal se habían recuperado completamente hasta alcanzar los niveles de bosque primario a los 40 y 90 años, respectivamente. Sin embargo, los bosques secundarios carecían de especies raras y presentaban una escasa abundancia de especies especialistas del bosque antiguo, lo que condujo a una recuperación incompleta de la composición de especies, incluso a 120 años de sucesión. También encontramos pruebas de que el predominio de un pionero longevo en las primeras etapas de la sucesión provocó una alteración de la estructura forestal y retrasó la recuperación de la diversidad y composición de especies más allá de un siglo después el abandono de las tierras. Nuestros resultados ilustran la importancia crítica de los bosques primarios y secundarios más antiguos para la conservación de la biodiversidad, dado que la recuperación de la composición de la comunidad puede llevar varios siglos, especialmente cuando un pionero longevo domina en la sucesión temprana.

Application of Gut Bacterial Profiling Information in Precision Nutrition for Obesity and Weight Loss Management.

BACKGROUND: It has been suggested that the dysfunction of the gut microbiome can have deleterious effects on the regulation of body weight and adiposity by affecting energy metabolism. In this context, gut bacterial profiling studies have contributed to characterize specific bacteria associated with obesity. This review covers the information driven by gut bacterial profiling analyses and emphasizes the potential application of this knowledge in precision nutrition strategies for obesity understanding and weight loss management. SUMMARY: Gut bacterial profiling studies have identified bacterial families that are more abundant in obese than in nonobese individuals (i.e., Prevotellaeae, Ruminococcaceae, and Veillonellaceae) as well as other families that have been repeatedly found more abundant in nonobese people (i.e., Christensenellaceae and Coriobacteriaceae), suggesting that an increase in their relative amount could be an interesting target in weight-loss treatments. Also, some gut-derived metabolites have been related to the regulation of body weight, including short-chain fatty acids, trimethylamine-N-oxide, and branched-chain and aromatic amino acids. Moreover, gut microbiota profiles may play a role in determining weight loss responses to specific nutritional treatments for the precise management of obesity. Thus, incorporating gut microbiota features may improve the performance of integrative models to predict weight loss outcomes. KEY MESSAGES: The application of gut bacterial profiling information is of great value for precision nutrition in metabolic diseases since it contributes to the understanding of the role of the gut microbiota in obesity onset and progression, facilitates the identification of potential microorganism targets, and allows the personalization of tailored weight loss diets as well as the prediction of adiposity outcomes based on the gut bacterial profiling of each individual. Integrating microbiota information with other omics knowledge (genetics, epigenetics, transcriptomics, proteomics, and metabolomics) may provide a more comprehensive understanding of the molecular and physiological events underlying obesity and adiposity outcomes for precision nutrition.

Latin Dance Effects on Cardiorespiratory Fitness and Physical Function in Middle-Aged and Older Latino Adults.

We tested if a dance trial yielded improvements in physical function and cardiorespiratory fitness (CRF) in middle-aged/older Latino adults. Physical activity was assessed using the Community Healthy Activities Model Program for Seniors, physical function with the Short Physical Performance Battery (SPPB) protocol, and estimated CRF with the Jurca nonexercise test model. Multivariate analysis of covariance models found significant change in SPPB protocol total scores, F(1, 329) = 4.23, p = .041, and CRF, F(1, 329) = 5.16, p = .024, between the two study arms in favor of the dance group. Mediation models found moderate- to vigorous-intensity physical activity to mediate to mediate between group and SPPB scores (ß = 0.054, 95% confidence interval [0.0142, 0.1247]). Moderate- to vigorous-intensity physical activity and total physical activity were found to partially mediate between group and CRF (ß = 0.02, 95% confidence interval [-0.0261, 0.0751]), with the direct pathway no longer being significant (p > .05). This provides support for Latin dance programs to have an effect on SPPB protocol and CRF.

Pediatric and psychiatric models of autism care in Mexico: Differences in diagnostic tools and prescribed interventions.

Low- and middle-income countries face heterogeneity in the way clinicians' approach Autism Spectrum Disorder (ASD) diagnosis and treatment. The current study analyzes the diagnostic tools, laboratory tests, pharmacological and psychosocial interventions received by patients during the steps to diagnosis and treatment of two specialized care centers. Researchers interviewed families with a child with ASD receiving services at either a child psychiatric or a pediatric hospital. Of the total sample, 47% reported clinicians not using a diagnostic tool, 20% reported not receiving any psychosocial intervention, and 88% reported receiving a pharmacological prescription. Patients at the pediatric hospital were more likely to receive interventions with some components of Applied Behavioral Analysis, Early Start Denver Model, Treatment and Education of Autistic and Related Communication Handicapped Children, and Sensory integration therapy; while patients at the psychiatric hospital were more likely to undergo learning, daily living skills, and socialization therapies. Patients at the psychiatric hospital received significantly more requests to obtain auditory and vision tests whilst genetic testing and imaging were more common in the pediatric hospital. The range and variability in terms of diagnostic tools, laboratory tests, and treatment options observed for both sites reflect a lack of consensus. Recommendations to improve ASD diagnostic and treatment in Mexico are given.

The deinstitutionalization of children and adolescents in El Salvador's child protection system.

BACKGROUND: In 2010, El Salvador introduced legislation aimed at reforming the country's Child Protective System (CPS), with a focus on promoting deinstitutionalization. OBJECTIVE: The study aim was to explore the impact of deinstitutionalization on the Salvadoran CPS. PARTICIPANTS AND SETTING: The study was conducted in El Salvador, granting authors unique access to key informants with extensive experience in the country's CPS. Unlike the United States, which is divided into states, El Salvador is divided into departments, and CPS providers were recruited from all 14 departments. Focus groups were facilitated in the East, West, and Central zones to ensure representation from all regions. METHODS: Qualitative semi-structured interviews (n = 26) were conducted in June/July of 2019, which were then followed by focus groups (n = 4) in August 2019. The analysis of the data employed a combination of deductive and inductive thematic coding methods. RESULTS: CPS providers offered valuable insights, categorized into five main themes: (1) Strengths of El Salvador's CPS, (2) Deinstitutionalization policy encompassing socioenvironmental contextual factors, (3) Challenges in the deinstitutionalization process, including insufficient follow-up on deinstitutionalized children, (4) Recommendations from participants, highlighting the importance of enhancing stakeholder coordination/collaboration, and (5) The necessity for a paradigm shift, emphasizing the need to redefine the social contract on protecting children from child maltreatment. CONCLUSIONS: The Salvadoran CPS requires substantial systemic changes. Encouragingly, key informants have demonstrated a commitment to reform not only the deinstitutionalization process but also the broader CPS system in El Salvador including case management and quality of care in institutional settings.

Mixed success for carbon payments and subsidies in support of forest restoration in the neotropics.

Restoration of forests in low- and middle-income countries (LMICs) has the potential to contribute to international carbon mitigation targets. However, high upfront costs and variable cashflows are obstacles for many landholders. Carbon payments have been promoted as a mechanism to incentivize restoration and economists have suggested cost-sharing by third parties to reduce financial burdens of restoration. Yet empirical evidence to support this theory, based on robust, dynamic field sampling is lacking. Here we use large, long-term datasets from Panama to evaluate the financial prospects of three forest restoration methods under different cost-sharing and carbon payment designs where income is generated through timber harvests. We show some, but not all options are economically viable. Further work combining growth and survival data from field trials with more sophisticated financial analyses is essential to understanding barriers and realizing the potential of forest restoration in LMICs to help meet global carbon mitigation commitments.

Dietary Intake of Capsaicin and Its Association with Markers of Body Adiposity and Fatty Liver in a Mexican Adult Population of Tijuana.

Background: Capsaicin (CAP) is the main chemical component responsible for the pungency (burning pain) of the chili plant (capsicum spp.), whose metabolic functions include energy balance and fatty acid oxidation. The aim of this study is to analyze the association of dietary capsaicin consumption with markers of adiposity and fatty liver in a Mexican adult population. Methods: This cross-sectional/analytical study recruited 221 subjects aged 18 to 65 years who were resident in the city of Tijuana, Baja California, Mexico. The daily CAP intake was analyzed through a validated chili/CAP consumption questionnaire. Anthropometric and biochemical measurements were performed following standardized protocols. Adjusted Pearson's correlations were applied to analyze the association of CAP with adiposity and fatty liver markers. Results: In this study, the daily average consumption of CAP was 152.44 mg. The dietary CAP consumption positively correlated with BMI (r = 0.179, p = 0.003), hip circumference (r = 0.176, p = 0.004) and body adiposity index (r = 0.181, p = 0.001. Likewise, the daily CAP intake positively correlated with hepatic steatosis index (r = 0.158, p = 0.004), fatty liver index (r = 0.141, p = 0.003) and lactate dehydrogenase (r = 0.194, p = 0.016) after statistical settings. Conclusions: The results of this study suggest positive associations between dietary CAP consumption and the markers of body adiposity and fatty liver in a Mexican adult population.

Physiological adaptation and population dynamics of a nitrifying sludge exposed to ampicillin.

Antibiotics in wastewater treatment plants can alter the physiological activity and the structure of microbial communities through toxic and inhibitory effects. Physiological adaptation, kinetic, and population dynamics behavior of a nitrifying sludge was evaluated in a sequential batch reactor (SBR) fed with 14.4 mg/L of ampicillin (AMP). The addition of AMP did not affect ammonium consumption (100 mg NH4+-N/L) but provoked nitrite accumulation (0.90 mg NO2--N formed/mg NH4+-N consumed) and an inhibition of up to 67% on the nitrite oxidizing process. After 30 cycles under AMP feeding, the sludge recovered its nitrite oxidizing activity with a high nitrate yield (YNO3-) of 0.87 ± 0.10 mg NO3--N formed/mg NH4+-N consumed, carrying out again a stable and complete nitrifying process. Increases in specific rate of nitrate production (qNO3-) showed the physiological adaptation of the nitrite oxidizing bacteria to AMP inhibition. Ampicillin was totally removed since the first cycle of addition. Exposure to AMP had effects on the abundance of bacterial populations, promoting adaptation of the nitrifying sludge to the presence of the antibiotic and its consumption. Nitrosomonas and Nitrosospira always remained within the dominant genera, keeping the ammonium oxidizing process stable while an increase in Nitrospira abundance was observed, recovering the stability of the nitrite oxidizing process. Burkholderia, Pseudomonas, and Thauera might be some of the heterotrophic bacteria involved in AMP consumption.

Temporary Knockdown of p53 During Focal Limb Irradiation Increases the Development of Sarcomas.

Approximately half of patients with cancer receive radiotherapy and, as cancer survivorship increases, the low rate of radiation-associated sarcomas is rising. Pharmacologic inhibition of p53 has been proposed as an approach to ameliorate acute injury of normal tissues from genotoxic therapies, but how this might impact the risk of therapy-induced cancer and normal tissue injuries remains unclear. We utilized mice that express a doxycycline (dox)-inducible p53 short hairpin RNA to reduce Trp53 expression temporarily during irradiation. Mice were placed on a dox diet 10 days prior to receiving 30 or 40 Gy hind limb irradiation in a single fraction and then returned to normal chow. Mice were examined weekly for sarcoma development and scored for radiation-induced normal tissue injuries. Radiation-induced sarcomas were subjected to RNA sequencing. Following single high-dose irradiation, 21% of animals with temporary p53 knockdown during irradiation developed a sarcoma in the radiation field compared with 2% of control animals. Following high-dose irradiation, p53 knockdown preserves muscle stem cells, and increases sarcoma development. Mice with severe acute radiation-induced injuries exhibit an increased risk of developing late persistent wounds, which were associated with sarcomagenesis. RNA sequencing revealed radiation-induced sarcomas upregulate genes related to translation, epithelial-mesenchymal transition (EMT), inflammation, and the cell cycle. Comparison of the transcriptomes of human and mouse sarcomas that arose in irradiated tissues revealed regulation of common gene programs, including elevated EMT pathway gene expression. These results suggest that blocking p53 during radiotherapy could minimize acute toxicity while exacerbating late effects including second cancers. SIGNIFICANCE: Strategies to prevent or mitigate acute radiation toxicities include pharmacologic inhibition of p53 and other cell death pathways. Our data show that temporarily reducing p53 during irradiation increases late effects including sarcomagenesis.

Differential DNA Methylation from Autistic Children Enriches Evidence for Genes Associated with ASD and New Candidate Genes.

The etiology of Autism Spectrum Disorders (ASD) is a result of the interaction between genes and the environment. The study of epigenetic factors that affect gene expression, such as DNA methylation, has become an important area of research in ASD. In recent years, there has been an increasing body of evidence pointing to epigenetic mechanisms that influence brain development, as in the case of ASD, when gene methylation dysregulation is present. Our analysis revealed 853 differentially methylated CpG in ASD patients, affecting 509 genes across the genome. Enrichment analysis showed five related diseases, including autistic disorder and mental disorders, which are particularly significant. In this work, we identified 64 genes that were previously reported in the SFARI gene database, classified according to their impact index. Additionally, we identified new genes that have not been previously reported as candidates with differences in the methylation patterns of Mexican children with ASD.